On March 28, 1979, the worst nuclear exposure incident in U.S. history occurred near Harrisburg, PA. Small quantities of xenon and iodine radioisotopes were released into the environment from the Three Mile Island (TMI) nuclear power plant. The Pennsylvania Department of Health (PDoH) implemented a TMI Population Registry, including 32,135 individuals within a 5-mile radius of TMI, to track possible health effects to the local population. Although no increase in cancer mortality has been noted in this cohort, cancer incidence has not been tracked. Given the long latency period for the development of thyroid cancer after exposure to low-level radiation exposure, it is plausible that an increase in thyroid cancer incidence might just now be occurring. Retrospective analysis of the Pennsylvania Cancer Registry Dataset for Thyroid Cancer using the Epidemiological Query and Mapping System (EpiQMS) search engine. EpiQMS is an interactive health statistics Website that can produce numbers, rates, graphs, charts, maps, and county profiles using various demographic variables (age, sex, race, etc.) from birth, death, cancer, and population datasets for the state and counties or regions of Pennsylvania. Eighteen years of data (1985-2002) on thyroid cancer incidence were obtained from the PDoH. The three at-risk counties of Dauphin, York, and Lancaster were analyzed with regard to observed numbers of thyroid cancer cases versus expected incidence. Although the nuclear accident at TMI occurred in 1979, 1985 was chosen as the starting point for data analysis because that is when the PDoH began maintaining cancer incidence records. In the first year available for evaluation (1985), there were 11 new thyroid cancer cases in each of the at-risk counties (Dauphin, York, Lancaster). By 2002, the incidence had increased to 29 in Dauphin County, 81 in Lancaster County, and 69 in York County. The increase in thyroid cancer in Dauphin County is not above what would be expected for both the local population growth and the increase in thyroid cancer incidence in the U.S. population in general. Thyroid cancer incidence was greater than expected in York County for all but 1 year between 1995 and 2002. Lancaster demonstrated a marked increase in thyroid cancer incidence over expected norms throughout the study period. An increase greater than 50% was noted in certain years. Thyroid cancer incidence has not increased in Dauphin County, the county in which TMI is located. York County demonstrated a trend toward increasing thyroid cancer incidence beginning in 1995, approximately 15 years after the TMI accident. Lancaster County showed a significant increase in thyroid cancer incidence beginning in 1990. These findings, however, do not provide a causal link to the TMI accident.